Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis.
Leukotrienes, the biologically active metabolites of arachidonic acid, have been implicated in a variety of inflammatory responses, including asthma, arthritis and psoriasis. Recently a compound, MK-886, has been described that blocks the synthesis of leukotrienes in intact activated leukocytes, but has little or no effect on enzymes involved in leukotriene synthesis, including 5-lipoxygenase, in cell-free systems. A membrane protein with a high affinity for MK-886 and possibly representing the cellular target for MK-886 has been isolated from rat and human leukocytes. Here, we report the isolation of a complementary DNA clone encoding the MK-886-binding protein. We also demonstrate that the expression of both the MK-886-binding protein and 5-lipoxygenase is necessary for leukotriene synthesis in intact cells. Because the MK-886-binding protein seems to play a part in activating this enzyme in cells, it is termed the five-lipoxygenase activating protein (FLAP).
Dixon
R A
RA
Department of Molecular Biology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
Diehl
R E
RE
Opas
E
E
Rands
E
E
Vickers
P J
PJ
Evans
J F
JF
Gillard
J W
JW
Miller
D K
DK
D058927:5-Lipoxygenase-Activating Proteins; D000595:Amino Acid Sequence; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D015289:Leukotrienes / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D012516:Osteosarcoma; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; C548594:Alox5ap protein, rat; D002352:Carrier Proteins; D015289:Leukotrienes; D008565:Membrane Proteins; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase